Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective:To investigate the effects of multidisciplinary small-class teaching on expertise and skill acquisition and learning experience in standardized residency training in general surgery.Methods:Sixty residents of grade 2021 rotating in general surgery from January to August 2023 were divided into multidisciplinary teaching group ( n=30) and traditional teaching group ( n=30, to receive tradition one-on-one teaching). All the residents underwent a theoretical examination and Mini-Clinical Evaluation Exercise (Mini-CEX) skill assessment before admission, and the scores were compared between the two groups. At the end of training, the two groups were compared in terms of theoretical and Mini-CEX skill assessment scores and the degree of satisfaction with teaching. Statistical analysis was conducted using SPSS 26.0. Results:There were no significant differences in the theoretical assessment and Mini-CEX skill assessment scores before admission between the two groups ( P>0.05). At the end of training, the multidisciplinary teaching group had a significantly higher theoretical examination score [(88.15±3.45) vs. (72.25±4.36), P<0.05] and a significantly higher Mini-CEX score [(86.35±2.24) vs. (76.28±3.92), P<0.05] compared with the traditional teaching group. According to the survey, the residents in the multidisciplinary teaching group were more satisfied with teaching and more likely to recognize the teaching effects. Conclusions:Multidisciplinary small-class teaching can help improve the quality of standardized general surgery residency training on gastrointestinal tumor treatment, which is a highly accepted and effective attempt at standardized residency training.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Objective:To investigate the clinical significances of evaluation indexes of right heart function injury in patients with BCR-ABL-negative myroproliferative neoplasms (MPN).Methods:The clinical data of 208 patients with BCR-ABL-negative MPN diagnosed in the Second People's Hospital of Lianyungang and Jiangsu Province Hospital from January 2015 to August 2021 were retrospectively analyzed, including 63 cases of primary myelopathic fibrosis (PMF), 39 cases of polycytosis vera (PV) and 106 cases of essential thrombocythemia (ET). The clinical characteristics of patients and the examination results of hematological related indicators were compared among the three groups. The examination results of indexes of right heart function injury were analyzed, including echocardiography, brain natriuretic peptide, soluble growth stimulation expression gene-2 (sST-2), lactate dehydrogenase (LDH), D-dimer, ferritin, β 2-microglobulin, peripheral blood WT1 gene, CD34 + cell count, etc. Results:Of the 208 patients, 109 were male and 99 were female; the median age was 62 years old (23 years old, 89 years old). The differences in levels of hemoglobin, platelet count, D-dimer, LDH and ferritin among PMF, PV and ET patients were statistically significant (all P < 0.05). Color echocardiography was performed in 87 patients, including 26 cases of PMF, 19 cases of PV and 42 cases of ET. Pulmonary artery pressure increased in 69 cases (79.3%), left atrial diameter increased in 76 cases (87.3%), and diameter increased during right ventricular diastolic period in 59 cases (67.8%). There were significant differences in pulmonary artery pressure, left atrial diameter and diameter during right ventricular diastolic period among PMF, PV and ET patients (all P < 0.05). Pearson correlation analysis showed that pulmonary artery pressure was positively correlated with ferritin, LDH, sST-2 and age ( r values were 0.796, 0.768, 0.915 and 0.734, all P<0.05), while it was negatively correlated with platelet count ( r = -2.330, P = 0.034). Conclusions:For BCR-ABL-negative MPN patients, the increase of pulmonary artery pressure, ferritin and LDH and the decreased platelet count and hemoglobin may increase the probability of right heart function impairment. For BCR-ABL-negative MPN patients with the higher levels of ferritin, LDH, sST-2, age, and the lower level of platelet count, the pulmonary artery pressure may be higher.

Objective:To investigate the application value of stereotactic digital naviga-tion system assisted three-dimensional (3D) laparoscopic total mesorectal excision (TME) for rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of a healthy volunteer recruited by the Second Affiliated Hospital of Army Medical University and 3 patients who underwent stereotactic digital navigation system assisted 3D laparoscopic TME for rectal cancer in the Second Affiliated Hospital of Army Medical University from May to September 2019 were collected. The healthy volunteer was male, aged 25 years. Of the 3 rectal cancer patients, there were 2 males and 1 female, with the age of 48 years, 63 years and 67 years, respectively. Ten special patches were placed at the anterior superior iliac spine, pubic tubercle and pubic symphysis of the volunteer's bilateral inguen as skin reference points in intraoperative localization and system registration. On the day of operation, patients were placed 10 special patches as skin reference points according to the test results of the volunteer and were completed the enhanced scan of totally abdominal computed tomography examination. Seven fixed anatomical markers in the abdominal cavity of the patients, including abdominal aortic bifurcation, sacrum scapula, bilateral anterior superior iliac spine, bilateral intersection of ureter and iliac artery and median point of peritoneal reflection, were selected for verifying the accuracy of the correspondence between the instrument tip and the system image. Patients underwent 3D laparoscopic TME for rectal cancer assisted by stereotactic digital navigation system. Observation indicators: (1) test results; (2) surgical situations; (3) accuracy of stereotactic digital navigation system. Measurement data with normal distribution were represented as Mean± SD. Results:(1) Test results. The 10 skin reference points of the volunteer were successfully registered in the stereotactic digital navigation system, with the registration error of 2.8 mm. (2) Surgical situations. All the 3 patients underwent stereo-tactic digital navigation system assisted 3D laparoscopic TME for rectal cancer successfully. The operation time of the 3 patients were 193 minutes, 175 minutes, 210 minutes, respectively, in which the set time of the stereotactic digital navigation system were 34 minutes, 25 minutes, 45 minutes, respectively. The volume of intraoperative blood loss of the 3 patients were 60 mL, 30 mL, 80 mL, respectively. Results of postoperative pathological examination showed 3 patients with adenocar-cinoma, including 1 case with mucinous adenocarcinoma. The tumor diameter and the numbers of lymph nodes dissected of the 3 patients were 2.3 cm, 1.5 cm, 4.0 cm and 12, 12, 13, respectively. No patient had lymph node metastasis. The 3 patients in preoperative clinical TNM stage cT3bN0M0, stage cT4aN1M0, stage cT3bN1M0 were in yield pathological TNM stage ypT1N0M0, stage ypT4aN0M0, stage ypT2N0M0 after neoaduvant chemotherapy, respectively. No patient had complication, and the duration of postoperative hospital of the 3 patients was 7 days, 6 days, 7 days, respectively. (3) Accuracy of stereotactic digital navigation system. The registration errors of the skin reference points were 2.8 mm, 2.6 mm, 2.9 mm and the accuracy errors of the abdominal cavity reference points were (2.5±0.4)mm, (2.3±0.7)mm, (2.6±0.6)mm for the 3 patients.Conclusion:The stereotactic digital navigation system assisted 3D laparoscopic TME for rectal cancer is safe and feasible.

Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

Colorectal cancer is the fourth most malignant tumors in China, among which the left hemicolon cancer accounts for about 5%?6%. Due to the complex anatomy around the left hemicolon, being adjacent to the pancreas, spleen, kidney, ureter and other important organs, its vascular and nerve distribution is variably distributed, leading difficulties in laparoscopic radical surgery for left hemicolon cancer. In surgical practice, the 4K laparoscopic system has shown its features of high-definition amplification, good color reproduction, and clear anatomy, etc. However, there is still no clear consensus on its application in the radical resection for the left hemicolon cancer. The authors summarize clinical practice, explore the technique key points of 4K laparoscopic D 3 resection with complete mesocolic excision for the left hemicolon cancer.

Objective:To investigate the changes of related indicators of right heart hypofunction in patients with primary myelofibrosis (PMF).Methods:The clinical data of 55 PMF patients in the Second People's Hospital of Lianyungang in Jiangsu Province and Jiangsu Province Hospital from January 2015 to August 2019 were retrospectively analyzed. The differences in right heart function-related echocardiographic indexes and biochemical indexes between pre-fibrosis/early stage fibrosis patients and obvious stage fibrosis patients were compared. Single factor linear regression method was used to analyze the correlations of pulmonary artery pressure with biochemical indexes.Results:The hemoglobin level [119 g/L (47-224 g/L) vs. 78 g/L (33-182 g/L)] and platelet count [233×10 12/L (5×10 12/L-984×10 12/L) vs. 117×10 12/L (7×10 12/L-731×10 12/L)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (both P<0.05). Among 22 patients with complete results of cardiac ultrasound, 90.9% (20/22) patients had increased pulmonary artery pressure, 72.7% (16/22) patients had increased left atrial diameter, and 90.9% (20/22) patients had increased right ventricular diastolic diameter. There were no patients with abnormal ejection fraction. The pulmonary artery pressure [48 mmHg (46-90 mmHg) vs. 33 mmHg (20-50 mmHg) (1 mmHg = 0.133 kPa)], left ventricular diastolic diameter [46 mm (36-50 mm) vs. 47 mm (43-53 mm)] and fractional shortening rate [38.1% (36.0%-38.9%) vs. 35.4% (32.7%-37.8%)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (all P < 0.05). The pulmonary artery pressure of patients had positive correlations with age ( r = 0.590), serum ferritin (SF) ( r = 0.608), lactate dehydrogenase (LDH) ( r = 0.711) and soluble growth-stimulating expression gene 2 (ST-2) ( r = 0.580)(all P<0.05), and had negative correlation with platelet count ( r = -0.596, P = 0.003). Conclusion:PMF patients are prone to right heart hypofunction, the pulmonary artery pressure is higher in older patients and patients with high SF, LDH and ST-2 levels and low platelet count.